HIV post-exposure prophylaxis in the Emergency Department: a perspective from Singapore

Abstract

Background:

Exposures to human immunodeficiency virus (HIV) commonly arrive at the Emergency Department (ED) for evaluation of transmission risk and the necessity for post-exposure prophylaxis (PEP). PEP aims to prevent HIV after exposure. International recommendations exist to guide eligibility assessment and standardise prescribing practices.

Objective:

The primary objective was to describe the patient cohort receiving HIV PEP at the ED. The secondary objective was to assess the ED physicians’ adherence to the 2005 guidelines provided by US Centers for Disease Control and Prevention for HIV PEP.

Methods:

This retrospective study identified patients prescribed with PEP after presenting with potential HIV exposure to a tertiary hospital ED in Singapore over 2 years. The exposure type and characteristics, source patient characteristics, indications for PEP, HIV status on presentation and on follow-up were assessed. Institutional guidelines recommended tenofovir/emtricitabine (Truvada) and raltegravir as HIV PEP.

Results:

Twenty-seven patients received HIV PEP during the study period. The majority (81.5%) presented after occupational exposure, with fresh needlestick injury (44.4%) being the most common cause. Amongst all recipients, PEP was indicated in 22.2% and not in 18.5%.

Conclusions:

With international guidelines simplifying eligibility assessment and prescribing practices, accurate and evidence-based PEP provision should be implemented at the frontline in the ED. These may be encouraged by enforcement of specific workflows and physician education.

Keywords

Human immunodeficiency virus post-exposure prophylaxis emergency infectious disease

Introduction

Human immunodeficiency virus (HIV) post-exposure prophylaxis (PEP) aims to reduce the risk of HIV transmission through the use of antiretroviral (ARV) medications (Table 1). The efficacy of PEP in reducing the risk of HIV transmission has been reported to be in excess of 80%.^1,2 Commencement of PEP is time-sensitive and requires risk assessment that considers the source patient’s risk profile and the nature of exposure including the infectious material involved.

Table 1.

Possible regimens for antiretroviral (ARV) medications.

(a) Three-drug regimens include nucleoside analogues and integrase inhibitor are preferred. (i) Occupational exposure⁷ Tenofovir/emtricitabine + raltegravir Alternatives:
Combination of 1 drug/drug pair from left column + 1 drug pair from right column
Raltegravir	Tenofovir/emtricitabine
Ritonavir/ darunavir	Tenofovir/lamivudine
Ritonavir/atazanavir	Zidovudine/lamivudine
Ritonavir/lopinavir	Zidovudine/emtricitabine
Etravirine
Rilpivirine (ii) Non-occupational exposure⁸ Tenofovir/emtricitabine + raltegravir Alternatives: tenofovir/emtricitabine + ritonavir/darunavir (b) Two-drug regimens are effective but three-drug regimens are preferred.^9,10 Two-drug: tenofovir/emtricitabine, tenofovir/lamivudine or zidovudine/lamivudine Three-drug: as above in a(i)

Patients with potential HIV exposures, both occupational and non-occupational in nature, often present to the Emergency Department (ED) for evaluation and treatment. As such, it is imperative that attending ED physicians be familiar with performing a risk assessment to determine the need for PEP in these patients.^3,4 In spite of clear international guidelines on the indications for PEP prescription (Table 2), there still exists significant variation in PEP prescribing habits amongst ED physicians, suggesting a need for education to increase awareness.⁵

Table 2.

Indications for PEP prescription.

1. High risk exposure a. Needlestick b. Mucous membrane exposure c. Needle sharing d. Anal or vaginal intercourse e. Other (injury with non-needle sharp, blood exposure to an open wound, receptive oral intercourse, human bite causing broken skin)

2. High risk body fluid a. Blood b. Seminal, vaginal, or rectal secretions c. Other (e.g. cerebrospinal, synovial, amniotic fluid)

3. High risk source a. Known HIV b. MSM c. IDU d. Other (e.g. sex trade worker, partner with known HIV) e. Unknown source but assault

4. Presentation within 72 h

5. Not HIV-positive on presentation

Locally, approximately 450 new cases of HIV infections are reported every year.⁶ There is a growing national emphasis on public education to aid in prevention, early detection and timely treatment. Proper PEP prescription by healthcare practitioners plays a key complementary role to these efforts. As such, our study aims to address the existing knowledge gap in prevailing PEP prescribing behaviour amongst ED physicians in Singapore.

Methods

Setting

This study was conducted in an ED in Singapore with an attendance of about 135,000 patients a year. The facility is staffed by ED physicians accredited by the Specialist Accreditation Board of Singapore. Infectious disease (ID) physicians are available for phone consultation round the clock. A workflow for management of potential blood-borne disease exposure (including HIV) is available in this institution, which is administered by the staff clinic (for hospital staff during office hours) and the ED (for hospital staff after office hours and the general public). The institutional guidelines for PEP regimen include tenofovir/emtricitabine (Truvada) and raltegravir. Patients who are administered PEP following ED consultation are given a PEP ‘starter-pack’ which contains enough medication supply till the patient’s follow up appointment with the ID physician on the next working day. This could range from a 1-day supply for an appointment on the following day to a 3-day supply for an appointment after the weekend. The remaining course of medications is given after the ID consult, if deemed necessary.

Objectives

The primary objective was to describe the patient cohort receiving HIV PEP at the ED. The secondary objective was to assess the ED physician’s adherence to the 2005 Centers for Disease Control (CDC) guidelines for HIV PEP (Table 2). PEP is indicated if the exposure type, bodily fluid, and source were classified as high risk, and the patient had presented within 72 h of exposure. PEP would not be indicated if the patient fails to fulfil one or more of the criteria.

Study design

This study was carried out as a departmental audit of ED patients who received HIV PEP from 1 January 2014 to 31 December 2015. ED patients who were prescribed Truvada and raltegravir during this period were identified on the hospital electronic record system. A retrospective electronic chart review was then conducted for these patients. Data collected include patient demographics, type of exposure, time from exposure to ED consult, mechanism of exposure, type of fluid from source, HIV risk profile of source, type of HIV PEP prescribed in ED, concomitant PEP for other conditions prescribed in ED (e.g. for hepatitis B and hepatitis C), as well as the HIV, hepatitis B and hepatitis C status of patient at presentation and subsequent follow-up visits. Occupational exposure is defined as related to an individual’s scope of work, while non-occupational exposure is that not related to one’s job scope.

Data analysis

Microsoft Excel (Microsoft Office 2013) was utilised for data collection and analysis. Median and interquartile range (IQR) are presented for continuous variables, while count and percentage were obtained for categorical variables.

Results

We identified a total of 27 patients who received HIV PEP comprising of Truvada and raltegravir in the ED for possible HIV exposure within our study period. The baseline demographics of our study group is summarised in Table 3.

Table 3.

Baseline demographics of patients.

Median age (range)	29.1 (17–46)
Males, n (%)	16 (59.3)
Females, n (%)	11 (40.7)
Race, n (%)
Chinese	13 (48.1)
Indian	6 (22.2)
Malay	1 (3.7)
Others	7 (26)

HIV exposures presenting to our institution’s ED were predominantly occupational (n = 22, 81.5%) in nature. The most common occupational exposure in our cohort was fresh needlestick injury (n = 12, 44.4%), followed by abandoned needlestick injury (n = 3, 11.1%) and exposure of bodily fluids to mucous membranes (n = 3, 11.1%). The patients were most commonly exposed to blood (n = 21, 77.8%). More than one-third of the patients were exposed to a source with unknown HIV risk profiles. Table 4 describes the characteristics of HIV exposure amongst patients in our cohort.

Table 4.

Characteristics of HIV exposure.

Type of exposure, n (%)
Occupational	22 (81.5)
Non-occupational	5 (18.5)
Presentation to ED within 72 h of exposure, n (%)	16 (59.2)
Mechanism, n (%)
Fresh needlestick	12 (44.4)
Abandoned needlestick	3 (11.1)
Exposure to mucus membrane	3 (11.1)
Sharing needle with high risk source	0 (0)
Vaginal intercourse	2 (7.4)
Anal intercourse	1 (3.8)
Other high risk exposure	2 (7.4)
Other low risk exposure	2 (7.4)
Unknown	2 (7.4)
Exposure fluid, n (%)
Blood	21 (77.8)
Semen, vaginal, rectal secretions	3 (11.1)
CSF, synovial, amniotic fluid	3 (11.1)
Low risk fluids (saliva, urine, stool, emesis)	0 (0)
HIV risk profile of patient, n (%)
HIV positive	5 (18.5)
MSM	1 (3.7)
IVDU	2 (7.4)
Other	4 (14.8)
Non high risk	5 (18.5)
Unknown	10 (37.1)

In assessing the degree of adherence to the 2005 CDC guidelines, we found PEP prescription to be indicated in six cases (22.2%), not indicated in five (18.5%), and of unknown indication for over half of the cases (n = 16, 59.2%) due to inadequate information.

Concomitant prophylaxis for hepatitis B was started in the ED for two cases (7.4%), who were prescribed hepatitis B immunoglobulin and vaccination. There was also one patient who received acyclovir after potential exposure to herpes B virus.

HIV antibody screen was performed in 92.6% (n = 25) of the study population, who were all negative at presentation. On subsequent follow-up, 63.0% (n = 17) remained HIV-negative, while there were no further available records for the other patients.

Discussion

In this retrospective study of potential HIV exposures over 2 years, the majority of patients presented after occupational exposure (81.5%), higher than centres in the United States (68.9%).¹¹ Possible factors may include ease of access and higher awareness of PEP amongst healthcare employees. This notion is further supported by Merchant et al. who reported that over 90% of ED physicians had indicated experience in managing occupational exposure cases, while less than 50% indicated experience in treating non-occupational HIV exposure cases.⁵

According to the World Health Organization, 35.7 million health care workers are exposed to the risk of needlestick injury worldwide, of which 0.5% are HIV related exposures.¹² Fortunately, the transmission of HIV from needlestick injury is rare, with an incidence of 2.4–24 per million medical procedures, and a risk of infection of 0.23% if untreated.^13,14 Needlestick injuries occur as a result of handling suture needles, intravenous cannulas, injection needles and scalpels, often due to non-compliance to standard infection control precautions for safe handling and disposal of sharps.¹⁵ The risk of HIV transmission from exposure of bodily fluid to mucus membranes is uncertain due to the lack of epidemiological data but likely low with only sporadic reports in existing literature.

Occupational HIV exposure is a preventable workplace hazard, with a variable individual risk profile depending on the individual’s role, experience, types of procedure performed and setting in which they are performed.¹⁶ Regardless, all healthcare workers must adopt the same stringent attitude towards preventing occupational exposure by assuming that all patient contact are potentially infectious necessitating the routine use of appropriate personal protective equipment and hand hygiene. Most importantly, all sharps should be carefully handled and disposed of. A stringent infection control programme with regular training is important, along with making sure personal protective equipment and safety devices are readily available for use. There should also be a process of surveillance for reporting as under-reporting can be a barrier to timely and effective PEP. Ultimately, while PEP is effective, efforts should really be targeted at initial prevention of occupational exposures.

The comparatively lower percentage of non-occupational exposures may represent lower public awareness of the role that the ED can play in such exposure, or may be telling of other barriers to access, e.g. cultural preference to visit non-emergency settings (e.g. private clinics). Increased awareness of PEP and reduction of barriers are pertinent areas to be addressed. For the ED physician, it is important to remain familiar with the assessment and management of non-occupational exposures, even if these are encountered less frequently.

The ED is a port of call for individuals after potential HIV exposure, due to its ability to provide round-the-clock time-sensitive evaluation and management of body fluid exposures.^11,17 Emergency practitioners should be familiar with the nature of presentation of such patients to the ED, and the guidelines used for assessment and management of exposures. In the interest of evidence-guided best practices for patient care, adherence to such guidelines is of paramount importance.

We felt that documentation of certain aspects of the case history – more precisely, the characteristics of exposure – could be improved. The time from exposure to ED visit was not documented in more than one-third of cases despite it being an essential factor in determining the indication for HIV PEP. If this were to be ‘unknown’, the indication for PEP would be correspondingly unclear.¹¹ Contributing factors to poor documentation may include a comparatively lower volume of post-exposure HIV cases compared to other ED conditions causing a lack of familiarity, the lack of an institutional protocol specific to HIV encounters, or a gap in knowledge.

To encourage essential parts of the case history to be documented, the authors suggest that an institution-wide template be used for cases identified at triage as potential HIV exposure cases. Technology can be harnessed to incorporate an electronic history-taking sheet with mandatory answer fields. This would minimise omission of certain aspects of the history, as with the current free-text situation; important components of the history can then be sought and recorded accordingly. The template can also serve as a guide to remind attending physicians as such encounters are infrequent. Additional measures include having continuing medical education for physicians to standardise the assessment and management of such cases. Even with ID consultation available to the ED physician, a thorough initial history is essential as it provides the necessary foundation upon which sound clinical decisions can be based.

HIV PEP is indicated only if all high-risk criteria are met. It was concerning that in our study, only 6 (22.2%) had a definite indication for PEP. Treatment was not indicated in 5 cases (18.5%) based on the 2005 CDC guidelines, although ID consult was obtained over the phone in all these cases. This may represent a judgement call by the ID specialist, or a deviation from usual protocol by the ID specialist. In another 16 cases (59.2%), the indication was unclear due to unknown or missing information. The overwhelming majority (14 cases, 87.5% of the unclear indications) had an ID consult, and therefore may represent a judgement call by the specialist. Two cases (12.5% of the unclear indications) did not have an ID consult; the ED senior made the call for HIV prophylaxis. This would represent a deviation from protocol by the ED physicians.

It was possible that ED physicians may choose to err on the side of caution due to the long-term implications of chronic HIV infection. Similarly, ID physicians may have a lower threshold to initiate HIV PEP when approached via a phone consult. It would be desirable to devise more clearly defined protocols for HIV exposures managed in the ED, with input from both ED and ID physicians. Information such as the commencement of therapy can be included, to reduce variability in management. This would provide us with an institution-wide stance on management. ED physicians should then adhere to these best clinical practices. Nonetheless, we acknowledge areas of ambiguity may still exist. Therefore, ID consult should still be available to aid decision making for HIV PEP in the ED.

Baseline HIV testing was recommended for the exposed individual at the time of presentation to the ED.^1,18 This was performed via rapid diagnostic tests (e.g. enzyme-linked immunosorbent assay (ELISA)) that typically yield results within a few hours. Two cases (7.4%) in our study did not undergo initial HIV testing. This may reflect a lack of knowledge amongst ED attending physicians of the information required for adequate assessment of the need for PEP. There would be implications as prescription of ARV for PEP would not be indicated if the individual was already HIV positive at time of exposure. The cessation of ARV in a HIV positive patient can lead to the development of resistance to ARV. Therefore, such individuals should be referred to ID physician for further assessment, treatment and follow-up.

Guidelines have advised that exposed individuals should be followed-up with a repeat ELISA for anti-HIV antibodies at 4–6 weeks, 3 months and 6 months after exposure if the source is HIV positive or of unknown HIV status.¹⁸ However, repeat testing is not required if the source patient is determined to be HIV negative.¹⁹ Considering these recommendations, there were 10 cases (37.0%) who had no follow-up HIV testing done after the initial ED visit. The rationale for this was not immediately clear and could not be better assessed in our study.

Adherence to therapy was a concern that had been reflected in studies originating from other centres internationally. It was known that completion of the full 28-day course was needed for maximum benefit,^1,18 and previous simian studies had shown that shorted courses of PEP were linked to incomplete protection.²⁰ However, patient attrition between the ED visit and the follow up appointment with the ID physician may result in non-completion of the 28-day course of PEP. While the scope of this study did not include assessment of completion of the 28-day PEP regime, the authors felt that further work assessing adherence to a full PEP course would be necessary. An alternative model of care may include having a primary care provider (PCP) to deliver all the PEP care.²¹ A PCP who already has rapport with the patient may be less intimidating for the patient to approach for consultation or support following the exposure. However, it is important for patients and healthcare providers to remember that the ID visit provides more than simply continuing the course of PEP medication – these specialists evaluate the patient for medication-related side effects and toxicity, screen for associated exposures, and provide valuable counselling to the patient.

To ensure holistic assessment of the patient, physicians should remember to assess for other blood-borne diseases, e.g. hepatitis B and C.¹⁸ Unfortunately, further evaluation of the management of this group of patients was beyond the scope of our study, as our population was derived only from patients who were prescribed HIV PEP.

Limitations

This study was conducted at a single tertiary centre in Singapore, yielding a rather limited sample size which may not be representative of demographics for the rest of Singapore, nor representative of the regional hospital patient type. There was also the possibility that patients encountering exposures did not present to the ED, but instead went to a clinic, or did not seek medical attention at all: our study would not have visibility of this population.

Evaluation of the data was hampered by the retrospective nature of the study as some entries lacked detail: time lapse between exposure and ED presentation, type of fluid and source HIV risk profile. As there was no institutional workflow specific to cases of HIV exposures, there was a possibility that the ED may not be adequately identifying – and by relation, appropriately managing – high-risk versus non high-risk cases. Furthermore, reasons behind any deviation from protocol by ED and ID physicians at time of ED encounter could not be elucidated.

As the study population was derived from the patients who were prescribed Truvada and raltegravir, patients who were prescribed other drugs for PEP would not be included in our study. While an alternative method of deriving the population would be to filter patients based on ICD codes, this could be less precise as the patient encounter could be classified under different ICD codes at the physician’s discretion, making it difficult to ensure inclusion of all cases.

Anti-retroviral drugs used for PEP are associated with side effects – Truvada is associated with a risk of renal toxicity and most three-drug regimens may cause transaminitis.^1,18,22 Therefore, it is important that a thorough assessment of eligibility for PEP be carried out, and anti-retroviral therapy only commenced according to best practice guidelines. Indiscriminate prescription without a clear indication can result in increased rates of side effects and toxicity in a population that may not derive proven benefits from therapy. The report of side effects experienced by patients from the ‘starter-pack’ pack of PEP prescribed from the ED, as well as during the full 28-day course of PEP, was beyond the scope of our study.

Conclusion

Our study found that HIV exposure patterns in our institution consist mainly of occupational exposures. This reflected the lack of awareness and barriers to seeking treatment amongst individuals with non-occupational exposure. The decision matrix for prescription of PEP did not adhere to current recommendations. A proposed future direction will be for the development of a more clearly defined institutional protocol specific for HIV exposure with details on drug use and management, as well as physician education to increase awareness of current guidelines and protocols. This would reduce institutional variability in prescription, and non-adherence to published guidelines.

Footnotes

Funding

This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

Availability of data and materials

The data and materials are not available to the public due to Personal Data Protection Act.

Authors’ contributions

JHP conceived the idea. GNLW carried out the data collection and analysis. All authors were involved in paper writing and approved the final version for publication.

Conflict of interest

The authors declare that there are no conflicts of interest.

Informed consent

Not applicable.

Ethical approval

Not applicable.

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